The goal of this work is to study mechanisms of pathogenesis of murine retroviruses. Previous studies showed that two closely related variants of Friend murine leukemia viruses differed in their ability to induce hemolytic anemia and splenomegaly shortly after inoculation into newborn mice. In vitro construction of recombinants between these strains demonstrated that this difference was due to differences in the viral envelope gene. DNA sequencing has revealed only 2 sequence differences between these strains, and site-specific mutagenesis has now identified a single amino acid responsible for this alteration in pathogenesis.